Exosomes mediated the delivery of ochratoxin A-induced cytotoxicity in HEK293 cells

Liye Zhu; Haomiao Wang; Jieyu Yuhan; Boyang Zhang; Hongyu Li; Charles Asakiya; Kunlun Huang; Xiaoyun He; Wentao Xu

doi:10.1016/j.tox.2021.152926

Exosomes mediated the delivery of ochratoxin A-induced cytotoxicity in HEK293 cells

Toxicology. 2021 Sep:461:152926. doi: 10.1016/j.tox.2021.152926. Epub 2021 Sep 3.

Authors

Liye Zhu¹, Haomiao Wang², Jieyu Yuhan², Boyang Zhang¹, Hongyu Li², Charles Asakiya², Kunlun Huang², Xiaoyun He², Wentao Xu³

Affiliations

¹ Key Laboratory of Precision Nutrition and Food Quality, Department of Nutrition and Health, China Agricultural University, Beijing, 100083, China; College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, 100083, China.
² College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, 100083, China.
³ Key Laboratory of Precision Nutrition and Food Quality, Department of Nutrition and Health, China Agricultural University, Beijing, 100083, China. Electronic address: xuwentao@cau.edu.cn.

PMID: 34481902
DOI: 10.1016/j.tox.2021.152926

Abstract

Ochratoxin A (OTA) is one of the mycotoxins, which widely pollutes food systems and seriously threatens human health. OTA's target organ is the kidney. Exosome, as one of the extracellular vesicles, could be secreted by all kinds of cells. It contains different proteins, nucleic acid, and lipid, which are decided by their donor cells and could be uptake by the recipient cells, release their contents, and affect the recipient cell's life activity. In this study, a 24 h-treatment with 5 μM OTA was found to significantly reduce the cell viability of HEK293 cells and meanwhile to provide a sufficient quantity of exosomes, thus this concentration and time were selected for subsequent experiments. In addition, exosomes extracted by ultracentrifugation had higher purity, fewer impurities, and uniform morphology than that by the ExoQuick-TC kit. Furthermore, these exosomes increased ROS levels and decreased mitochondrial membrane potential in HEK293 cells. By RNA-seq, the cytotoxicity mechanisms induced by OTA-treated HEK293 cell-derived exosomes (EXO-OTA) and OTA were mainly the metabolism of proteins and the cell cycle respectively. Also, it proved that exosomes deliver partial OTA-induced cytotoxicity.

Keywords: Cytotoxicity; Exosomes; Ochratoxin A; Toxicology; Transcriptomics.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cell Cycle / drug effects
Cell Survival / drug effects*
Environmental Pollutants / toxicity
Exosomes / metabolism*
HEK293 Cells
Humans
Membrane Potential, Mitochondrial / drug effects
Ochratoxins / toxicity*
Reactive Oxygen Species / metabolism

Substances

Environmental Pollutants
Ochratoxins
Reactive Oxygen Species
ochratoxin A